This invention relates to ion accelerators. In particular, the invention relates to an ion acceleration apparatus and method for use in mass spectrometry, such as time of flight mass spectrometry.
Mass spectrometry is an analytical methodology used for quantitative elemental analysis of materials and mixtures of materials. In mass spectrometry, a sample of a material to be analyzed called an analyte is broken into particles of its constituent parts. The particles are typically molecular in size. Once produced, the analyte particles are separated by the spectrometer based on their respective masses. The separated particles are then detected and a xe2x80x9cmass spectrumxe2x80x9d of the material is produced. The mass spectrum is analogous to a fingerprint of the sample material being analyzed. The mass spectrum provides information about the masses and in some cases quantities of the various analyte particles that make up the sample. In particular, mass spectrometry can be used to determine the molecular weights of molecules and molecular fragments within an analyte. Additionally, mass spectrometry can identify components within the analyte based on the fragmentation pattern when the material is broken into particles. Mass spectrometry has proven to be a very powerful analytical tool in material science, chemistry and biology along with a number of other related fields.
A specific type of mass spectrometer is the time-of-flight (TOF) mass spectrometer. The TOF mass spectrometer (TOFMS) uses the differences in the time of flight or transit time through the spectrometer to separate and identify the analyte constituent parts. In the basic TOF mass spectrometer, particles of the analyte are produced and ionized by an ion source. The analyte ions are then introduced into an ion accelerator that subjects the ions to an electric field. The electric field accelerates the analyte ions and launches them into a drift tube or drift region. After being accelerated, the analyte ions are allowed to drift in the absence of the accelerating electric field until they strike an ion detector at the end of the drift region. The drift velocity of a given analyte ion is a function of both the mass and the charge of the ion. Therefore, if the analyte ions are produced having the same charge, ions of different masses will have different drift velocities upon exiting the accelerator and, in turn, will arrive at the detector at different points in time. The differential transit time or differential xe2x80x98time-of-flightxe2x80x99 separates the analyte ions by mass and enables the detection of the individual analyte particle types present in the sample.
When an analyte ion strikes the detector, the detector generates a signal. The time at which the signal is generated by the detector is used to determine the mass of the particle. In addition, for many detector types, the strength of the signal produced by the detector is proportional to the quantity of the ions striking it at a given point in time. Therefore, the quantity of particles of a given mass often can be determined also. With this information about particle mass and quantity, a mass spectrum can be computed and the composition of the analyte can be inferred.
In a time of flight mass spectrometer (TOFMS), the ion accelerator accepts a stream of ions from an ion source and accelerates the analyte ions by applying an electric field. The velocity of a given ion when it exits the ion accelerator is proportional to the square root of the accelerating field strength, the square root of the charge of the ion, and inversely proportional to the square root of the mass of the ion. Thus, ions with the same charge but differing masses are accelerated to differing velocities by the ion accelerator.
In addition to accelerating the analyte ions, the ion accelerator pulse modulates 25 the ion stream. The term xe2x80x9cpulse modulationxe2x80x9d as used herein refers to breaking the ion stream into a series of ion bunches or xe2x80x9cpacketsxe2x80x9d, each packet being individually accelerated by action of the ion accelerator. The individual packets are accelerated and allowed to drift to the detector one packet at a time. To accomplish the pulse modulation, the ion accelerator collects ions produced by the ion source in an input or fill region for a period of time. The period or time interval during which ions are collected is known as the fill period or fill interval. The ion accelerator periodically releases the collected ions from the fill region into an acceleration region. The period when the ions are released from the fill region into the acceleration region is known as the pulse period or duration. The sequential fill and pulse periods produce packets of ions traveling in the drift region and striking the detector. The separation in time between the packets is designed to enable the measurement of the differential TOFs of the various analyte ions. Ion accelerators are sometimes also referred to as a xe2x80x9cpulserxe2x80x9d or an xe2x80x9cion storage modulatorxe2x80x9d due to the pulse modulation that they impart on the analyte ion stream.
A widely used, conventional ion accelerator used in mass spectrometry is based on a design first proposed by Wiley and Mclaren (W. C. Wiley and I. H. Mclaren, xe2x80x9cTime-of-Flight Spectrometer with Improved Resolution,xe2x80x9d The Review of Scientific Instruments, vol. 26, no. 12, December, 1955, pp. 1150-1157) incorporated herein by reference. A description of a more contemporary version of the conventional accelerator based on the Wiley-Mclaren design is provided by Dodonov et al (A. F. Dodonov, et al, xe2x80x9cElectrospray Ionization on a Reflecting Time-of-Flight Mass Spectrometer,xe2x80x9d in Time-of-Flight Mass Spectrometry, ed. Robert J. Cotter, ACS Symposium Series 549, American Chemical Society, Washington, D.C., 1994, Chapter 7, pp. 108-123) incorporated herein by reference. The mechanical configuration of the ion accelerator is illustrated in FIG. 1. A schematic of the conventional ion accelerator is illustrated in FIG. 2.
The ion accelerator comprises a stack or sequentially located plurality of thin metal plates or electrodes separated by insulating spaces or spacers. The conventional ion accelerator further comprises a pair of high voltage pulse generators, 22 and 23, a fixed high voltage bias source 24 and a multi-tap voltage divider 20.
The stack of electrodes comprises a first electrode 10, a first grid 12, a second grid 13, a third grid 14, and a plurality of guard frames 16. The first electrode 10 is a solid conductive plate called a pulser plate or pulser electrode. The grids 12, 13, and 14 are conductive plates each of which has a porous, conductive screen or wire mesh covering a hole or opening that penetrates from one side of the grid to the other. The guard frames 16 are also conductive plates with a hole similar to that of the grids 10-14 except the hole in the guard frames 16 is not covered with a screen.
In the ion accelerator, the electrodes are ordered such that the pulser electrode 10 is followed by the first and second grids 12, 13. The second grid 13, in turn, is followed by a plurality of guard frames 16 that, in turn, are followed by the third grid 14. A space between the pulser electrode 10 and the first grid 12 is called a fill region 17. The holes in the grids 12-14 and the guard frames 16 are aligned in the stack to produce a channel or path from the fill region 17 to the third grid 14. The channel is called the acceleration region 18.
As depicted in the schematic illustrated in FIG. 2, the conventional ion accelerator comprises the first high voltage pulse generator 22 connected to the pulser electrode 10 and the second high voltage pulse generator 23 connected to the second grid 13. The high voltage bias source 24 is connected to third grid 14. The high voltage bias source 24 is also connected to an input port of the multi-tap voltage divider 20. Each of the taps or output ports of the voltage divider 20 is connected, in turn, to one of the plurality of guard frames 16. Each of the guard frames 16 is, therefore, biased by the voltage divider such that the magnitude of voltage potential of a given guard frame 16 is less than that of the guard frames 16 closer to the third grid 14. The first grid 12 is connected to ground potential.
The voltage from the fixed high voltage bias source 24 applied to the third grid 14 and applied to the plurality of guard frames 16 through the voltage divider 20 produces an electric field in the acceleration region 18. The polarity of the voltage produced by the fixed high voltage bias source 24 is such that the resulting electric field in the accelerating region 18 produces a force that causes the ions to accelerate towards the third grid 14.
During operation, the conventional ion accelerator cycles or switches between two states or periods known as the xe2x80x9cfill periodxe2x80x9d and the xe2x80x9cpulse periodxe2x80x9d, respectively. During the fill period, analyte ions having a charge are injected into the fill region 17 between the pulser plate 10 and the first grid 12. The analyte ions are produced by an ion source 26 and are induced to move into the fill region 17 under the influence of a voltage potential difference between the ion source 26 and the average voltage of the first grid 12 at ground potential and the pulser electrode 10 at approximately ground potential during the fill period. In addition, during the fill period a small voltage potential is applied to the second grid 13 by the second pulse generator 23. The small voltage potential has the same polarity as that of the charge on the analyte ions. The small potential applied to the second grid creates a potential gradient or barrier directed away from the acceleration region 18. This potential gradient prevents analyte ions from escaping or leaking from the fill region 17 into the acceleration region 18 during the fill period. An important feature of the conventional ion accelerator is its ability to prevent the leakage of analyte ions into the acceleration region 18 during the fill period by virtue of the presence of this potential gradient.
The pulse period commences once enough analyte ions have entered the fill region. During the pulse period, a large voltage pulse is applied to the pulser electrode 10 to xe2x80x9cpushxe2x80x9d the ions out of the fill region 17 and into the acceleration region 18. The voltage pulse has the same polarity as the analyte ions thereby imparting a repulsive force to the ions in the fill region 17. At the same time, an opposite polarity voltage pulse is applied to the second grid 13 by the second pulse generator 23. The potential difference between the pulser plate 10 and the second grid 13 during the application of these pulses establishes an electric field oriented such that the analyte ions are induced to move out of the fill region 17 and into the acceleration region 18. Ideally the ions move as a tightly spaced group or packet.
Once in the acceleration region 18, the electric field created by the application of the voltage bias to the third grid 14 and by way of the voltage divider 20 to the guard frames 16, accelerates the analyte ions toward the third grid 14. As noted above, the high voltage bias source 24 supplies this voltage bias. The accelerated ions ultimately pass through the screen of the third grid 14 to enter the drift region of the TOFMS not shown in FIGS. 1 and 2.
The relationship between the voltage potentials applied to the pulser electrode 10, the grids 12-14 and the guard frames 16 for the conventional ion accelerator is illustrated in FIG. 3 and FIG. 4. In FIG. 3 the relative voltage levels in a conventional ion accelerator having n guard frames 16 is illustrated. In FIG. 3 the voltage level is represented by the y-axis and the relative locations of the plates in the stack are illustrated on the x-axis. The voltages applied to the pulser electrode 10 are labeled P. The voltages applied to the first grid 12, the second grid 13, and the third grid 14 are labeled G1, G2 and G3 respectively. The voltages used to bias the n guard frames are labeled F1-Fn. The voltages for both the fill period and the pulse period are shown. The voltage levels shown are relative since the specific levels are a function of the specific TOFMS design and given analysis situation and would be readily determined by one skilled in the art.
FIG. 4 illustrates the relative voltages applied to the pulser electrode 10, first grid 12 and second grid 13, as a function of time. The voltages associated with the pulser electrode 10 are illustrated in the sub-plot labeled xe2x80x9cPulserxe2x80x9d. The voltages associated with the first grid 12 are illustrated in the sub-plot labeled xe2x80x9cGrid 1xe2x80x9d and voltages associated with the second grid 13 are illustrated in the sub-plot labeled xe2x80x9cGrid 2xe2x80x9d. In FIG. 4, voltage is shown on the y-axis with time on the x-axis. In each of the subplots of FIG. 4, the fill period is represented as the time interval tf and the pulse period is represented by the time interval tp. Notice that the first grid 12 (Grid 1) is essentially at zero volts during both the fill period and the pulse period.
The sensitivity and precision of the TOFMS depend on the ability of the ion accelerator to produce sharply defined pulses or packets of ions. To produce sharply defined pulses, the ion accelerator must minimize the number of ions that move or leak from the fill region 17 to the acceleration region 18 during the fill period. Additionally, the ion accelerator must be able to move ions from the fill region 17 to the acceleration region 18 in a short period of time during the pulse period. The conventional ion accelerator utilizes two synchronized high voltage pulse generators, 22 and 23, to accomplish the pulse modulation of the ion stream. These pulse generators are expensive to manufacture due to the typical voltage levels involved and the rise and fall times required to produce the desired ion pulses. In addition, circuitry must be provided to synchronize the pulse generators so that the voltage pulses occur simultaneously and to produce well defined ion pulses. Finally, in the conventional ion accelerator, the second pulse generator 23 must also be capable of producing the necessary opposite polarity bias voltage that is applied to the second grid 13 during the fill period thereby preventing the analyte ions from leaking in the acceleration region 18 prior the onset of the pulse period.
Thus, it would be advantageous to have an ion accelerator for use in a TOFMS that had only one pulse generator but exhibited minimal leakage during the fill period and that still produced sharply defined pulses during the pulse period. Such an ion accelerator would be lower in cost and higher in reliability than conventional ion accelerators while still maintaining the measurement sensitivity required for modern TOFMS.
The present invention provides an ion acceleration apparatus and method, which can be used in mass spectrometry, that utilize a single pulse generator while incorporating the advantages and performance characteristics of the state-of-the-art conventional ion accelerators.
In one aspect of the invention, an ion acceleration apparatus is provided that comprises a plurality of conductive plates in a spaced apart, stacked relationship. The plurality of plates comprises a pulser electrode and a plurality of grids. The pulser electrode and a third grid of the plurality grids form the outside ends of the stack with a first grid and a second grid interposed therebetween. The first grid is adjacent to the pulser electrode and a space between the pulser electrode and the first grid forms a fill region of the ion acceleration apparatus. A space between the second grid and the third grid forms an acceleration region that is adjacent to the fill region.
According to this aspect of the invention, analyte ions, having a charge polarity, are collected in the fill region during a fill period and the collected analyte ions are accelerated in the acceleration region toward the third grid at an output end of the stack during a pulse period. During the fill period, the electrode and the first grid each has a fill voltage with a polarity opposite to the charge polarity of the analyte ions, and during the pulse period the electrode and the first grid each has a pulse voltage with a polarity that is the same as the charge polarity of the analyte ions. The second grid has zero voltage and the third grid has a voltage with a polarity that is opposite the charge polarity of the analyte ions during both the fill period and the pulse period.
Preferably, the plurality of plates further comprises a plurality of guard frames, also known as frame units, interposed between the second grid and the third grid. The second grid is adjacent to a first guard frame of the plurality of guard frames and the third grid is adjacent to a last guard frame of the plurality of guard frames. Moreover, each of the pulser electrode, grids and guard frames are electrically insulated and spaced apart from one another preferably by insulating spacers. In addition, each grid and guard frame has a through hole, such that when stacked together an aligned channel or acceleration path is formed through the stack between the second grid and the third grids. Preferably, the holes in the grids are covered by a porous mesh or screen.
The ion acceleration apparatus further comprises a power source for generating voltages during the fill period and the pulse period. The power source preferably comprises a pulse generator for supplying the fill voltage and the pulse voltage to the electrode and to the first grid and a voltage source for supplying voltage to the third grid, and preferably to the plurality of guard frames. More preferably, the power source further comprises a first voltage divider connected between the pulse generator and the first grid for providing lower magnitude replicas of the fill voltage and the pulse voltage to the first grid than is supplied to the pulser electrode. In addition, the power source still further comprises a second voltage divider connected between the voltage source and the plurality of guard frames, such that the voltage applied to each guard frame by the voltage source increases in magnitude from the first guard frame to the last guard frame.
In another aspect of the invention, a method of pulse modulating and accelerating analyte ions using the ion acceleration apparatus described above is provided. During the fill period, the power source applies a fill voltage to the pulser electrode and the first grid. The analyte ions from an ion source enter the fill region where the analyte ions remain until a pulse voltage applied to the pulser electrode and first grid launches them into the acceleration region toward the third grid. The fill voltage is a small magnitude voltage potential of polarity opposite to that of the polarity of the charge on the analyte ions. The second grid is maintained at zero potential and the third grid has a constant voltage applied thereto of a polarity opposite to the polarity of the charge on the analyte ions. Preferably, each frame of the plurality of guard frames also has a progressively increasing magnitude voltage constantly applied thereto. The polarity of the voltage applied to the guard frames is opposite to that of the polarity of the charge on the analyte ions. The magnitude of the constant voltage applied to the third grid is greater in magnitude than the magnitude of voltage applied to the last guard frame of the plurality of guard frames located nearest to the third grid.
During the pulse period, the power source applies a voltage pulse to the pulser electrode and the first grid of the same polarity as the polarity of the charge of the analyte ions. The analyte ions that have collected in the fill region are launched or caused to move into the acceleration region. The voltages on the second grid, the plurality of guard frames and the third grid are constant and do not change during or between the pulse period and the fill period.
In still another aspect of the invention, a mass spectrometer (MS) is provided that utilizes the ion acceleration apparatus and method described above instead of conventional ion accelerators and methods. The MS of the invention comprises the conventional components of a MS, such as an ion source, an ion drift region and an ion detector. Moreover, the MS of the invention further comprises the ion acceleration apparatus of the present invention. When used in time-of-flight mass spectrometry, the time-of-flight mass spectrometer (TOFMS) of the invention provides comparable sensitivity to the measurement capability of state-of-the-art TOFMS at a lower cost and reduced complexity by virtue of the absence of a second pulse generator and associated synchronization circuitry.
In the present invention, a small same-polarity pulse (relative to pulser electrode) is applied to the first grid instead applying a complementary-opposite polarity pulse to the second grid, as is conventionally done. Advantageously, a simple voltage divider connected to the pulse generator is used to obtain the small same polarity pulse and therefore, a separate opposite polarity pulse generator is not needed.
Another feature of the ion acceleration apparatus of the present invention is that the second grid is used essentially as a first xe2x80x9celectrodexe2x80x9d in xe2x80x9ca string of electrodesxe2x80x9d or the plurality of guard frames. As mentioned above, each guard frame of the plurality of guard frame is connected to sequential taps of a voltage divider and the second grid is connected to ground potential. This greatly simplifies the circuitry needed to generate the voltages needed to bias the guard frames and the second grid. In fact, the bias voltages required can be generated using a simple, linear voltage divider, for example. One skilled in the art would readily recognize alternative methods for generating these bias voltages that are equivalent to using a voltage divider.
Moreover, when a small bias of opposite polarity to the polarity of the analyte ions is applied on the pulser electrode and similarly on the first grid during the xe2x80x9cfillxe2x80x9d period, advantageously, the invention provides a gating action that is created to prevent incoming ions from spilling or leaking into the acceleration region prior to the launch of an ion packet. By preventing ions from leaking into the acceleration region, the gating action provides a significant reduction in baseline noise. Decreasing baseline noise, in turn, increases the signal to noise ratio and thereby increases the sensitivity of the TOFMS.